Published online before print May 1, 2003, doi: 10.1161/01.RES.0000074906.98021.55
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Submitted on August 14, 2002
Revised on April 3, 2003
Accepted on April 22, 2003
Leprdb Diabetic Mouse Bone Marrow Cells Inhibit Skin Wound Vascularization but Promote Wound Healing
Vesna Stepanovic ;
From the Departments of Exercise Science (V.S., O.A., C.J., G.C.S.) and Dermatology (M.D.), University of Iowa, Iowa City.
* To whom correspondence should be addressed. E-mail: gina-schatteman{at}uiowa.edu.
Bone marrow stem cells participate in tissue repair processes and may have roles in skin wound repair. Diabetes is characterized by delayed and poor wound healing, and type 1 diabetes seems to lead to stem cell dysfunction. Hence, stem cell dysfunction could contribute to poor healing, and stem cell-based therapies may be efficacious in diabetic wounds. We investigated the potential of exogenous stem cells to promote skin healing and possible effects of type 2 diabetes on stem cell function. Mouse bone marrow cells from nondiabetic and diabetic mice were enriched for putative stem cells and injected under skin wounds of nondiabetic or type 2 diabetic Leprdb mice. Using histology and morphometry, vascularization and healing in treated and untreated mice were analyzed. We anticipated a correlation between improved wound healing and vascularization, because therapies that increase tissue vascularization tend to enhance wound healing. Our data indicate that exogenous nondiabetic bone marrow-derived cells increase vascularization and improve wound healing in Leprdb mice but have little effect on nondiabetic controls. In contrast, Leprdb-derived marrow cells inhibit vascularization but promote wound healing in Leprdb mice. Thus, adult stem cell function may be impaired by type 2 diabetes; the ability to promote vascularization and wound healing are distinct functions of bone marrow cells; and neovascularization and wound healing may not be tightly coupled. Additionally, we observed little incorporation of injected cells into wound structures, suggesting that improved healing is mediated through mechanisms other than direct differentiation and incorporation of the cells.
Key words: bone marrow • stem cells • angiogenesis • wound healing • type 2 diabetes
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